The University of Tokyo · 생화학·유전·분자생물학
요시오 ヤマウチ 교수의 연구실은 콜레스테롤 대사와 지질 호메오스타시스를 중심으로, 특히 ABCA1 수송체를 통한 고밀도리포프로테인(HDL) 형성과 세포 내 지질 운반 메커니즘을 연구하고 있습니다. 암세포의 지방생성 현상과 관련된 SREBP 전사인자 및 PI3K-Akt-mTOR 경로의 기능, 그리고 세포외 소포(EVs)를 통한 세포 간 신호 전달 메커니즘에도 깊이 관여하고 있습니다. 특히 지질 대사와 관련된 수송체, 효소, 신호전달 경로의 상호작용을 분자생물학적·세포생물학적 접근으로 규명하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
ATP-binding cassette transporter A1 (ABCA1) plays an essential role in the helical apolipoprotein-mediated assembly of high density lipoprotein, and the apolipoporteins stabilize ABCA1 against calpain-mediated degradation during the reaction ((2002) J. Biol. Chem. 277, 22426-22429). Protein kinase C (PKC) inhibitors suppressed both ABCA1 stabilization and cellular lipid release mediated by apolipoprotein A-I (apoA-I) but not ABCA1 increase by calpain inhibitors. The increase of ABCA1 and the cel
The lipogenic phenotype is a metabolic hallmark of cancer cells. Sterol regulatory element-binding proteins (SREBP) are key transcriptional factors to regulate biosynthesis of cholesterol and fatty acids. It has been poorly understood how the lipogenic phenotype in cancer cells is regulated and how it augments their malignant properties. Here we describe roles of the melanoma antigen ganglioside GD3 and phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR complex 1 (mTORC1) signaling in the regulation
Differential regulation has been suggested for cellular cholesterol and phospholipid release mediated by apolipoprotein A-I (apoA-I)/ABCA1. We investigated various factors involved in cholesterol mobilization related to this pathway. ApoA-I induced a rapid decrease of the cellular cholesterol compartment that is in equilibrium with the ACAT-accessible pool in cells that generate cholesterol-rich HDL. Pharmacological and genetic inactivation of ACAT enhanced the apoA-I-mediated cholesterol releas
Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and are present in the blood, their identity is poorly characterized <i>in vivo</i>, limiting the identification of their origin in the blood. Since skeletal muscle is the largest organ in the body, it could substantially contribute to circulating EVs as their source. However, due to the lack of defined mar
Cellular cholesterol homeostasis involves sterol sensing at the endoplasmic reticulum (ER) and sterol export from the plasma membrane (PM). Sterol sensing at the ER requires efficient sterol delivery from the PM; however, the macromolecules that facilitate retrograde sterol transport at the PM have not been identified. ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol and phospholipid export to apolipoprotein A-I for the assembly of high density lipoprotein (HDL). Mutations in ABC
Cholesterol is a vital lipid molecule for mammalian cells, regulating fluidity of biological membranes, and serving as an essential constituent of lipid rafts. Mammalian cells acquire cholesterol from extracellular lipoproteins and from <i>de novo</i> synthesis. Cholesterol biosynthesis generates various precursor sterols. Cholesterol undergoes metabolic conversion into oxygenated sterols (oxysterols), bile acids, and steroid hormones. Cholesterol intermediates and metabolites have diverse and i
